The Effect of Azithromycin on Relapse in Patients with Moderate-Severe Chronic Graft Versus Host Disease (CGVHD)

BACKGROUND A recent U.S. Food and Drug Administration (FDA) safety communication (Aug 2018) warned prescribers of the risk of relapse in patients receiving azithromycin as prophylaxis for bronchiolitis obliterans syndrome (BOS) following hematopoietic cell transplant (HCT). However, the FDA warning was based upon a single multicenter trial, in which patients were randomized to receive azithromycin for 2 years, starting at the time of conditioning. We now examine relapse rates in a cohort of patients treated with azithromycin for management of moderate-severe CGVHD. PATIENT POPULATION A retrospective review of our HCT database (2010-2017) identified 239 patients (median age 55 years, range 4-72) with moderate-severe CGVHD following an allogeneic HCT for a primary hematologic malignancy. NIH consensus criteria (2015) were used for CGVHD grading. Patients were divided into 2 cohorts, a) those receiving an extended course of azithromycin (≥ 14 days) for CGVHD management (cohort 1, n=86) and b) those who did not (cohort 2, n=153). Patients in cohort 2 either did not receive any azithromycin (n=122) or had received an abbreviated ( RESULTS Decreased rates of relapse and improved survival were noted for patients treated with azithromycin for CGVHD. At 2 years, the cumulative incidence of relapse was 2% (95% CI:1-9%) for patients in cohort 1 vs 16% (95% CI: 11-23%) in cohort 2, p=0.001. Overall survival (2-year OS) in cohort 1 was 93% (95%CI: 88-99%) vs 78% (95% CI:72-85%) for cohort 2, p=0.003. Overall, 7 of 86 (8.1%) CGVHD patients treated with an extended course of azithromycin (cohort 1) have relapsed, the median time to relapse 876 days (range 379-1303) post-HCT. In comparison, 28 of 153 (18.3%) in cohort 2 have relapsed, a median 371 days (range 98-1252) post-HCT. CONCLUSION The use of azithromycin for the management of moderate to severe CGVHD was not associated with an increased risk of relapse in patients undergoing HCT for a hematologic malignancy. Azithromycin therapy for patients with CGVHD should not be contra-indicated in this patient population.